Deconvolution and interruption of the cancer-neuro-immune axis facilitating brain metastases

癌症-神经-免疫轴的解卷积和中断促进脑转移

• 批准号: 10706491
• 负责人: Melanie Hayden Gephart
• 金额: $ 147.68万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-21 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10706491
• 关键词: Address; Advocate; Biology; Brain; Brain Neoplasms; CRISPR library; Cancer Patient; Clinical; Clinical Trials; Communication; Communities; Data; Dedications; Deterioration; Development; Diagnostic; Disease model; Ensure; Exclusion; Experimental Models; Foundations; Goals; Human; Immune system; Immunotherapy; In Vitro; Incidence; Interruption; Malignant Neoplasms; Mediator; Metastatic malignant neoplasm to brain; Methods; Microglia; Modeling; Molecular; Mus; Neoplasm Metastasis; Neuroimmune; Neurologic; Office of Administrative Management; Organoids; Patient risk; Patients; Physicians; Primary Neoplasm; Production; Productivity; Quality of life; Research; Sampling; Scientist; Site; Specimen; Technology; Testing; Therapeutic; Translating; Translations; Tropism; Tumor Tissue; Work; brain cell; data management; design; experience; glycoproteomics; high throughput screening; human disease; human tissue; improved; in vivo Model; innovation; insight; interest; multidisciplinary; neoplastic cell; neuropathology; new therapeutic target; novel; organizational structure; programs; synergism; therapy resistant; tool; tumor; tumor microenvironment

1 ABSTRACT – OVERALL COMPONENT 2 3 The development of brain metastases, experienced by up to 40% of cancer patients, marks a clear inflection 4 point in survival and quality of life. The inaccessibility of brain tumor tissue has stymied progress in our 5 understanding and treatment of brain metastases, and patients are regularly excluded from clinical trials. The 6 Stanford Brain Metastasis Consortium has unified brain and cancer experts in the singular goal of improving our 7 understanding and treatment of brain metastases, a currently increasing yet underserved subset of cancer 8 patients. To accomplish the above goal, we have: (1) designed an organizational structure that supports 9 scientists in our integrated work; (2) developed highly innovative and complementary Projects to understand 10 and disrupt the cancer-neuro-immune axis supporting brain metastases; and (3) created NeuroPathology 11 and ToolKit Cores to make human specimens and cutting-edge technologies readily accessible to participating 12 scientists. We expect to identify and target key mediators of brain metastasis, with therapeutic benefit for 13 patients. 14 Little is known about the distinct mechanisms that drive tumor cells to the brain and allow them to grow in this 15 unique microenvironment, supported in part by normal brain cells. Streamlined access to human brain 16 specimens, combined with innovations in modeling and manipulation of the tumor microenvironment, create this 17 collaborative opportunity for fundamental advancement. Our expert, integrated team of productive collaborators 18 aims to understand how the intrinsic features of tumor cells (Project 1), resident microglia (Project 2), and the 19 systemic immune system (Project 3) contribute to the onset and progression of brain metastases. These projects 20 are facilitated by centralized access to human patient brain metastases samples (NeuroPathology Core), and 21 novel, multiplexed analyses and disease modeling (ToolKit Core). Our multidisciplinary physician Consultant 22 Network provides clinical insight and helps in the rapid translation of our findings into clinical trials for patients 23 with brain metastases. The Administrative and Data Management Core will provide the operational support 24 necessary to successfully achieve the goals of the program. Our Patient Advocates help to integrate and 25 communicate our work to the greater scientific and patient communities. 26 We have formed one of the few groups with the expertise, interest, and capacity to address the underlying 27 mechanisms of and therapeutic opportunities for brain metastases. Only through this combined synergy would 28 this project be possible. These innovative methods will ensure our findings are reflective of and translatable to 29 the human disease, enabling our multidisciplinary team to lay the foundation for diagnostic and therapeutic 30 advancements.

1个摘要 - 整体组件 2 3多达40％的癌症患者经历的脑转移的发展标志着明显的弯曲 生存和生活质量的4点。脑肿瘤组织的无法获得性在我们的 5对脑转移的理解和治疗以及患者经常被排除在临床试验之外。这 6斯坦福大脑转移财团拥有统一的大脑和癌症专家，以改善我们的奇异目标 7理解和治疗脑转移，这是当前增加但服务不足的癌症子集 8位患者。为了实现上述目标，我们有：（1）设计一个支持的组织结构 9个科学家在我们的综合工作中； （2）开发了高度创新和完整的项目以了解 10并破坏支撑脑转移的癌症 - 尼罗 - 免疫轴； （3）创建神经病理学 11和工具包芯使人类标本和尖端技术容易访问 12个科学家。我们希望识别和瞄准脑转移的关键介体，并具有治疗益处 13例患者。 14关于将肿瘤细胞驱动到大脑的不同机制知之甚少，并允许它们在此生长 15独特的微环境，部分由正常脑细胞支持。流线型进入人脑 16个标本，结合了肿瘤微环境建模和操纵的创新，创造了这个 17基本进步的协作机会。我们的专家，集成的产品合作者团队 18旨在了解肿瘤细胞的内在特征如何（项目1），居民小胶质细胞（项目2）和 19系统性免疫系统（项目3）有助于脑转移的发作和进展。这些项目 20是通过集中访问人类患者脑转移样本（神经病理学核心）和 21新型，多重分析和疾病建模（工具包核心）。我们的多学科身体顾问 22网络提供临床见解，并有助于将我们的发现快速转化为患者的临床试验 23脑转移。行政和数据管理核心将提供运营支持 24成功实现该计划的目标所必需的。我们的患者拥护者有助于整合和 25将我们的工作传达给更大的科学和患者社区。 26我们组成了少数几个具有专业知识，有趣和能力来解决基础的团体之一 27脑转移的机制和治疗机会。只有通过这种联合协同作用 28这个项目是可能的。这些创新的方法将确保我们的发现反映并可以翻译成 29人类疾病，使我们的多学科团队能够为诊断和治疗奠定基础 30个进步。